Bisguanidines and fungicides containing them

ABSTRACT

The present invention relates to bisguanidine derivatives of the formula I ##STR1## where R 1  and R 2  are each, independently of one another, hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkenyl; or cycloalkyl which has 5-12 carbon atoms in the ring and may be substituted, or benzyl which may be substituted, with the proviso that only one of R 1  and R 2  can be hydrogen; or 
     R 1  and R 2  are, together with the atoms which they substitute, a heterocyclic ring which may be substituted; 
     X is CH 2 , O, a single bond, NH, N-alkyl or N-benzyl whose phenyl ring may be substituted, 
     n is 5 to 8, 
     and their plant-compatible acid addition salts and their metal complexes and fungicides containing these compounds.

This is a division of application Ser. No. 07/743,160 filed on Aug. 9,1991 now U.S. Pat. No. 5,242,948.

The present invention relates to novel bisguanidines with a fungicidalaction and to fungicides containing them.

GB 1,114,155 discloses the compound ##STR2## and its fungicidal action.

Also known to have a fungicidal action areα,ω-bis(3,4-dichlorobenzylguanidino)alkanes (A. F. McKay et al., J. Med.Chem. 6 (1963) 587). ##STR3##

Other guanidinas are known from U.S. Pat. No. 3,488,898, DE 39 22 232.2,EP 338,430, G.B. 935,614 and EP 406,899. However, the action of thesecompounds is not a1ways satisfactory, especially at low applicationrates and concentrations.

We have now found that bisguanidine derivatives of the formula I##STR4## where

R¹ and R² are each, independently of one another, hydrogen, C₅ -C₁₀-alkyl, C₃ -C₁₀ -alkenyl, C₃ -C₁₀ -alkynyl, C₁ -C₈ -alkoxy-C₂ -C₈-alkyl, C₃ -C₁₀ -haloalkenyl; or cycloalkyl which has 5-12 carbon atomsin the ring and can carry up to three of the following substituents:hydroxyl, C₁ -C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl and C₁ -C₈-alkoxy-C₁ -C₈ -alkyl; or benzyl which can be substituted up to threetimes by C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkoxy, it being possible for thesubstituent also to carry a hydroxyl or C₁ -C₆ -alkoxy group; or thebenzyl is substituted by C₁ -C₁₀ -haloalkyl, with the proviso that onlyone of R¹ and R² can be hydrogen; or

R¹ and R₂ are, together with the atoms which they substitute, a 5- to11-membered heterocyclic ring which can be substituted once to threetimes by C₁ -C₁₀ -alkyl or C₁ -C₈ -alkoxy-C₁ -C₈ -alkyl;

X is CH₂, O, a single bond, NH, N-(C₁ -C₁₀ -alkyl) or N-benzyl whosephenyl can be substituted once to three times by C₁ -C₁₀ -alkyl, C₁ -C₁₀-alkoxy, C₁ -C₁₀ -haloalkyl

n is 5 to 8,

and their plant-compatible acid addition salts and their metalcomplexes, have an excellent fungicidal action against phytopathogenicfungi.

If R¹ or R² is hydrogen, the compounds can exist in tautomeric formswhich are covered by the invention.

With a view to their fungicidal action, the preferred compounds arethose in which the substituents have the following meanings:

R¹ , R² hydrogen, with the proviso that not less than one of R¹ and R²is different from hydrogen; C₅ -C₁₀ -alkyl, especially pentyl,1,1-dimethylpropyl or 2,4,4-trimethyl-2-pentyl; C₃ -C₁₀ -alkenyl or C₃-C₁₀ -alkynyl, especially allyl, dimethylallyl or 2-butynyl; C₁ -C₈-alkoxy-C₂ -C₈ -alkyl, especially methoxyethyl, tert.-butoxyethyl ormethoxypropyl; C₃ -C₁₀ -haloalkenyl, especially 3-bromo-2-propenyl,2-bromo-2-propenyl or 3-chloro-2-propenyl; cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl and cyclododecyl, it being possible for these tocarry up to three of the following:

hydroxyl;

C₁ -C₁₀ -alkyl, especially methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec.-butyl, tert.-butyl, 1,1-dimethylpropyl or2,4,4-trimethyl-2-pentyl;

C₁ -C₁₀ -alkoxy, especially methoxy, ethoxy, isopropoxy, n-butoxy,tert.-butoxy or octyloxy; C₁ -C₄ -haloalkyl, especially trifluoromethylor pentafluoroethyl;

C₁ -C₈ -alkoxy-C₁ -C₈ -alkyl, especially methoxymethyl, ethoxymethyl,methoxyethyl, tert.-butoxymethyl or 1-methoxy-1-methylethyl; or benzyl,which can carry up to three of the following substituents:

C₁ -C₁₀ -alkyl, especially methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec.-butyl, tert.-butyl, 1,1-dimethylpropyl,2,3-dimethylpropyl, 1,1,2-trimethylpropyl, 2-hydroxy-2-propyl or2-methoxy-2-propyl;

C₁ -C₁₀ -alkoxy, especially methoxy, ethoxy, isopropoxy, n-butoxy,tert.-butoxy or octyloxy; C₁ -C₁₀ -haloalkyl, especially trifluoromethylor pentafluoroethyl;

particularly preferred for R¹ and R₂ are hydrogen, with the proviso thatnot less than one of R¹ and R² is different from hydrogen, cyclopentyl,cyclohexyl, cycloheptyl, 2-methylcyclohexyl, 3-methylcyclohexyl,3-trifluoromethylcyclohexyl, 3,3-dimethylcyclohexyl,4-tert.-butylcyclohexyl, 4-methylbenzyl, 4-ethylbenzyl,4-isopropylbenzyl, 4-tert.-butylbenzyl, 4-(1,1,2-trimethylpropyl)benzyl,2,4-dimethylbenzyl, 4-methoxybenzyl, 4-tert.-butoxybenzyl or3,4-dimethoxybenzyl;

R¹ and R² are, together with the atoms which they substitute, a 5- to11-membered heterocyclic ring, especially an imidazolinyl,tetrahydropyrimidyl, tetrahydro-1,3-diazepinyl, hexahydro-1,3-diazocinylor hexahydro-1,3-diazoninyl, it being possible for these to carry up tothree of the following substituents:

C₁ -C₁₀ -alkyl, especially methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec.-butyl, tert.-butyl, 1,1-dimethylpropyl or2,4,4-trimethyl-2-pentyl;

C₁ -C₈ -alkoxy-C₁ -C₈ -alkyl, especially methoxymethyl, ethoxymethyl,methoxyethyl, tert.-butoxymethyl or 1-methoxy-1-methylethyl;

particularly preferred for R¹ and R² are imidazolinyl,tetrahydropyrimidyl, 4,4-dimethyltetrahydropyrimidyl,5-tert.-butyltetrahydropyrimidyl or5-ethyl-5-propylhexahydro-1,3-diazocinyl

X is CH₂, O, a single bond, NH, N-(C₁ -C₁₀ -alkyl), especially N-methyl,N-ethyl, N-propyl, N-isopropyl, N-butyl, N-isobutyl, N-sec.-butyl,N-tert.-butyl or N-1,1-dimethylpropyl, N-benzyl whose phenyl can besubstituted by C₁ -C₁₀ -alkyl, especially methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec.-butyl, tert.-butyl, 1,1-dimethylethyl,1,1-dimethylpropyl, 2,3-dimethylpropyl, 1,1,2-trimethylpropyl, C₁ -C₁₀-alkoxy, especially methoxy, ethoxy, isopropoxy, n-butoxy, tert.-butoxyor octyloxy, C₁ -C₁₀ -haloalkyl, especially trifluoromethyl orpentafluoroethyl, or halogen, especially fluorine, chlorine or bromine;particularly preferred for X are CH₂, NH, N-methyl, N-ethyl, N-benzyl,N-4-tert.-butyl-benzyl, N-4-(1,1,2-trimethylpropyl)benzyl,N-4-methoxybenzyl, N-4-tert.-butoxybenzyl, N-4-chlorobenzyl,N-4-fluorobenzyl or a single bond; n is 5 to S, i.e. 5, 6, 7 or 8.

Also preferred are compounds in which R¹ and R² are, independently ofeach other, hydrogen or cycloalkyl, as defined above, and X is NH.Compounds in which R¹ and R² together denote imidazolinyl ortetrahydropyrimidinyl and X is NH or a single bond are also preferred.

Suitable acid addition salts are the plant-compatible salts of thoseacids which do not impair the fungicidal action of I, e.g. iodides,chlorides, bromides, sulfates, dodecyl sulfates, nitrates, carbonates,phosphates, borates, formates, acetates, propionates, benzoates,oxalates, naphthalenesulfonates, dodecylbenzenesulfonates, lactates,citrates and the salts with the saccharin anion.

Suitable metal complexes are those of copper, zinc, tin, manganese,iron, cobalt or nickel. The complexes are preferably prepared from thefree bases I and the salts with mineral acids, for example the chloridesor sulfates, of the metals.

The bisguanidines I can be prepared in a variety of ways, the followingmethods being preferred:

a) Preparation from Isothiuronium Salts and Diamines ##STR5##

In these formulae, R³ is benzyl or C₁ -C₄ -alkyl, e.g. methyl or ethyl,and Y, is chloride, bromide, iodide, sulfate, methosulfate,methanesulfonate or tosylate.

The starting compounds II and III are known or can be obtained in aknown manner (for the isothiuronium salts, see Houben-Weyl, Methoden derOrganischen Chemie, 4th edition, Vol. IX, pp. 900 et seq.).

The reaction of isothiuronium salts with diamines which is shown in thediagram and is known (e.g. A. V. Bogatskii et al., Khim.-Farm. Zh. 17(1983) 308; CA 98 215574z) to give bisguanidine compounds I.HY' ispreferably carried out in polar solvents such as alcohols, ketones,ethers, nitriles, dimethyl sulfoxide, N-methylpyrrolidone,dimethylformamide or dimethylacetamide.

The reaction is generally carried out with from 2.0 to 4.0 moles,particularly preferably 2.0 moles, of isothiuronium salt II per mole ofdiamine III. It is also possible to have a tertiary amine such astriethylamine present as additional base. In this case, equimolaramounts of additional base and of isothiuronium salt are preferablyemployed.

The reaction can be carried out at from 20° C. to the boiling point ofthe solvent, preferably from 60° to 130° C.

The reaction is preferably carried out under atmospheric pressure.

Anion exchange can be used to obtain salts with other anions or, byreplacement by hydroxyl ions, the free bases I.

b) Preparation from Aminoiminomethanesulfonic Acids and Diamines##STR6##

The starting compounds IV are known or can be prepared from thioureaderivatives in a conventional manner (e.g. C. A. Maryanoff et al., J.Org. Chem., 51 (1986) 1882).

Suitable temperatures for the reaction are from 0° C. to the boilingpoint of the solvent.

The ratios of amounts and the pressure are the same as for method a).

The solvents are the same as for method a) but acetonitrile is veryparticularly preferred.

c) Preparation from Carbodiimides and Diamines ##STR7##

The starting compounds V are known or can be prepared by known processes(cf. e.g. M. Mikolaiczyk, Tetrahedron 37 (1981) 233).

It is advisable to employ for the reaction 2 moles of carbodiimide V permole of diamine III, but it is preferable to use a small excess of amineor carbodiimide, of up to about 10%, over the 1:2 ratio.

Suitable solvents for the reactions are hydrocarbons such as hexane ortoluene, short-chain alcohols such as isopropanol or tert.-butanol,amides such as dimethylformamide or nitriles such as acetonitrile.

The temperature and the pressure are the same as for method a).

d) Preparation from Imidocarbonates and Amines ##STR8##

When Z=0 in this formula, R⁴ is cyano, benzoyl or methanesulfonyl, andR⁵ is phenyl, and when Z=S, R⁴ is cyano and R⁵ is methyl.

The reaction of imidocarbonates with two amines is known (cf. e.g. A.Buschauer, Arzneim.-Forsch./Drug. Res., 37 (1987) 1003, 1008; Arch.Pharm., 321 (1988) 281) and is carried out in two separate stages. Theimidocarbonate is preferably reacted with the first amine in achlorohydrocarbon such as dichloromethane, an ether such as diethylether or tetrahydrofuran, a short-chain alcohol such as methanol orisopropanol, a water/alcohol mixture such as water/methanol or a nitrilesuch as acetonitrile. The reaction of the product with the second amineis then carried out in a polar solvent such as methanol, ethanol,isopropanol, tert.-butanol, pyridine or acetonitrile.

It is advisable to employ for the reactions 1.0 mole of amine VIIa orVIIb and 0.5 mole of diamine III per mole of imidocarbonate VI, but asmall excess of amine, of up to about 10%, is preferably used.

The temperature and pressure are the same as for method a). Theresulting compounds are hydrolyzed in a conventional manner,advantageously in a mineral acid or an organic carboxylic acid at, forexample, 70° to 120° C. Preferably used is 2 to 10M hydrochloric acid or50 to strength acetic acid.

The chlorides or acetates of the compounds I with R¹ or R² equal tohydrogen are obtained.

The free bases I are prepared as in method a).

e) Preparation from Cyanogen Bromide and Amines ##STR9##

Y' in these formulae is preferably chloride.

The reaction of cyanogen bromide with amines, which is known fromHouben-Weyl, Methoden der Org. Chemie, 4th edition, Vol. E4, p. 981, togive N-substituted cyanamides is preferably carried out in a two-phasesystem, e.g. water/dichloromethane, or else anhydrous in inert solventssuch as diethyl ether, tetrahydrofuran, dioxane, dichloromethane ortoluene. The reactions are preferably carried out at from -20° to +10°C.

The ratios of amounts and the pressure are the same as for method d).

The reaction of the N-substituted cyanamides VIIIa, VIIIb and IX, whichis known from Houben-Weyl, Methoden der Org. Chemie, 4th edition, Vol.E4, p. 609, with the hydrochlorides of the amines III, VIIa and VIIb ispreferably carried out without solvent at, for example, from 130° to250° C.

The amounts, the pressure and the preparation of the free bases I arethe same as for method d).

The compounds I with R¹ or R² equal to hydrogen are obtained.

The compounds of the formula I and the salts and metal complexes thereofare suitable as fungicides and are well tolerated by plants.

PREPARATION EXAMPLES Example 1

Method a) (Compound 11a)

1,13-Bis(3,3-dimethylcyclohexylguanidino)-7-azatridecane dihydroiodide##STR10##

A mixture of 16.4 g (0.050 mol) of3,3-dimethylcyclohexyl-S-methylisothiuronium iodide, 5.3 g (0.025 mol)of 1,13-diamino-7-azatridecane, 5 g (0.050 mol) of triethylamine and 15g of molecular sieves (4 Å) in 200 ml of anhydrous acetonitrile wasrefluxed under a nitrogen atmosphere for 48 hours, with elimination ofmethanethiol. The mixture was filtered hot and the compound was isolatedfrom the solution.

Yield: 93% of theory; melting point 120° C.

Precursor A1 3,3-Dimethylcyclohexyl-S-methylisothiuronium iodide##STR11##

A solution of 63 g (0.339 mol) of 3,3-dimethylcyclohexylthiourea and48.1 g (0.339 mol) of iodomethane in 100 ml of methanol was refluxed for1 hour. The solvent was distilled out under reduced pressure to leave ayellow resinous solid.

Yield: 58% of theory, melting point 80° C.

Precursor A2 3,3-Dimethylcyclohexylthiourea ##STR12##

59 g (0.42 mol) of benzoyl chloride were added dropwise over the courseof 10 minutes to a solution of 33 g (0.44 mol) of ammonium thiocyanatein 100 ml of absolute acetone. The mixture was refluxed for 10 minutesand then 50.8 g (0.40 mol) of 3,3-dimethylcyclohexylamine were addeddropwise, and the mixture was refluxed for a further 20 minutes and thenstirred into 500 ml of ice-water. The precipitated solid was filteredoff with suction, washed with water, dissolved in a hot mixture of 500ml of 10% strength sodium hydroxide solution and 125 ml of ethanol andrefluxed for 30 minutes. The reaction mixture was then diluted withice-water, and the pH was initially adjusted to 1 with concentratedhydrochloric acid and then to 9 with solid sodium bicarbonate. Theresulting precipitate was filtered off with suction, washed with waterand dried at 80° C. under reduced pressure.

Yield: 85% of theory; melting point 153° C.

Example 2 (Compound 18a) 1,17-Biscyclohexylguanidino-9-azaheptadecanetriacetate ##STR13##

10.2 g (0.011 mol) of 1,17-biscyclohexylguanidino-9-azaheptadecanedihydroiodide in 150 ml of methanol/water (1:1) were filtered through acolumn containing 250 g of ion exchanger (OH⁻ form). The free guanidinebase obtained after working up was dissolved in methanol and convertedinto the triacetate with excess glacial acetic acid.

Example 3

Method a) (Compound 16a)

1,17-Biscyclohexylguanidino-9-azaheptadecane dihydroiodide ##STR14##

A mixture of 30.0 g (0.10 mol) of cyclohexyl-S-methylisothiuroniumiodide, 13.6 g (0.05 mol) of 1,17-diamino-9-azaheptadecane, 10.0 g (0.10mol) of triethylamine and 20 g of molecular sieves (4 Å) in 300 ml ofanhydrous acetonitrile was refluxed under a nitrogen atmosphere for 5days, methanethiol being eliminated. The mixture was filtered hot andworked up as usual.

Yield: 43% of theory; melting point 170° C.

Precursor B1 Cyclohexyl-S-methylisothiuronium iodide ##STR15##

A solution of 62.0 g (0.392 mol) of cyclohexylthiourea and 55.7 g (0.392mol) of iodomethane in 300 ml of methanol was refluxed for 1 hour. Aftercooling to room temperature, the product was precipitated by addingmethyl tert.-butyl ether, filtered off with suction, washed with methyltert.-butyl ether and hexane and finally dried at 50° C. under reducedpressure.

Yield: 68% of theory; melting point 115°-120° C.

Precursor B2 Cyclohexylthiourea ##STR16##

295.5 g (2.1 mol) of benzoyl chloride were added dropwise over thecourse of 10 minutes to a solution of 165.0 g (2.2 mol) of ammoniumthiocyanate in 500 ml of absolute acetone. After refluxing for 10minutes, 198.9 g (2.0 mol) of cyclohexylamine were added dropwise, andthe mixture was refluxed for a further 20 minutes. It was then stirredinto 4 1 of ice-water, and the water was decanted off the oily product.The residue was dissolved in a hot mixture of 2 1 of 10% strength sodiumhydroxide solution and 500 ml of ethanol and refluxed for 30 minutes.The reaction mixture was then diluted with ice-water, and the pH wasadjusted initially to 1 with concentrated hydrochloric acid and then to9 with solid sodium bicarbonate. The resulting precipitate was filteredoff with suction, washed with water and dried at 80° C. under reducedpressure.

Yield: 78% of theory; melting point 135° C.

Example 4

Method c) (Compound 14a)

1,13-Bis(N,N'-dicyclohexylguanidino)-7-azatridecane trihydrochloride##STR17##

A mixture of 49.4 g (0.24 mol) of dicyclohexylcarbodiimide, 21.5 g (0.10mol) of 1,13-diamino-7-azatridecane and 400 ml of anhydroustert.-butanol was refluxed for 12 hours. The isolated oily product wasmixed with methanolic hydrochloric acid and the solvent was removed bydistillation under reduced pressure, leaving a colorless solid.

Yield: 26% of theory; melting point 140° C.

Example 5 (Compound 35b)1,12-Bis(2-amino-3,4,5,6-tetrahydropyrimidyl)dodecane diacetate##STR18##

30.0 g 10.048 mol) of1,12-bis(2-amino-3,4,5,6-tetrahydropyrimidyl)dodecane dihydroiodide in300 ml of methanol/water (1:1) were filtered through a column containing250 g of ion exchanger (OH⁻ form). The free guanidine base obtainedafter working up was dissolved in methanol and converted into thediacetate with excess glacial acetic acid.

Example 6

Method a) (Compound 34b)

1,12-Bis(2-amino-3,4,5,6-tetrahydropyrimidyl)dodecane dihydroiodide##STR19##

A mixture of 103.3 g (0.4 mol) of2-S-methyl-3,4,5,6-tetrahydropyrimidinium iodide, 40.0 g (0.2 mol) of1,12-diaminododecane, 20.2 g (0.2 mol) of triethylamine and 60 g ofmolecular sieves (4 Å) in 1 l of anhydrous acetonitrile was refluxedunder a nitrogen atmosphere for 16 hours, with elimination ofmethanethiol. The mixture was filtered hot and then worked up as

Yield: 81% of theory of a brown oil

IR (film): 3217, 2925, 2853, 1642, 1315 cm⁻¹

Precursor D1 2-S-Methyl-3,4,5,6-tetrahydropyrimidylisothiuronium iodide##STR20##

A solution of 50.0 g (0.431 mol) of perhydropyrimidinethione and 61.2 g(0.431 mol) of iodomethane in 200 ml of methanol was refluxed for 1hour. After cooling to room temperature, the product was precipitated byadding methyl tert.-butyl ether, filtered off with suction, washed withmethyl tert.-butyl ether and dried.

Yield 94% of theory; melting point 135° C.

                                      TABLE 1                                     __________________________________________________________________________     ##STR21##                                                                    Comp. No.                                                                           R.sup.1         R.sup.2                                                                              X             n HY    m.p./IR (film)                                                                [cm.sup.-1 ]               __________________________________________________________________________     1a   Cyclohexyl      H      NH            6 HCl   125° C.              2a   Cyclohexyl      H      NH            6 CH.sub.3 COOH                                                                       100° C.              3a   Cyclohexyl      H      NH            6 C.sub.2 H.sub.2 O.sub.4                                                             140° C.              4a   Cyclohexyl      H      NH            6 --                                5a   Cyclopentyl     H      NH            6 --                                6a   Cyclooctyl      H      NH            6 --                                7a   Cyclododecyl    H      NH            6 --                                8a   4-tert.-Butylcyclohexyl                                                                       H      NH            6 --                                9a   4-Isopropylcyclohexyl                                                                         H      NH            6 --                               10a   3-Trifluoromethylcyclohexyl                                                                   H      NH            6 --                               11a   3,3-Dimethylcyclohexyl                                                                        H      NH            6 HI    120° C.             12a   Cyclohexyl      Cyclohexyl                                                                           NH            6 --    2926, 2851, 1639,                                                             1448,                      13a   Cyclohexyl      Cyclohexyl                                                                           NH            6 CH.sub.3 COOH                                                                       3205, 3085, 2930,                                                             2855,                                                                         1612, 1573, 1450,                                                             1400,                                                                         1366, 1246                 14a   Cyclohexyl      Cyclohexyl                                                                           NH            6 HCl   140° C.             15a   Cyclohexyl      H      NH            8 --    3279, 3185, 2929,                                                             2854, 1652                 16a   Cyclohexyl      H      NH            8 HI    170-172° C.         17a   Cyclohexyl      H      NH            8 HCl   110° C.             18a   Cyclohexyl      H      NH            8 CH.sub.3 COOH                                                                        98-100° C.         19a   Cyclohexyl      H      NH            8 C.sub.2 H.sub.2 O.sub.4                                                             165-167° C.         20a   Cyclopentyl     H      NH            8 --                               21a   Cyclooctyl      H      NH            8 --                               22a   Cyclododecyl    H      NH            8 --                               23a   4-tert.-Butylcyclohexyl                                                                       H      NH            8 --                               24a   4-Isopropylcyclohexyl                                                                         H      NH            8 --                               25a   3-Trifluoromethylcyclohexyl                                                                   H      NH            8 --                               26a   3,3-Dimethylcyclohexyl                                                                        H      NH            8 --                               27a   Cyclohexyl      Cyclohexyl                                                                           NH            8 --                               28a   Cyclohexyl      H      single bond   5                                  29a   Cyclopentyl     H      single bond   5                                  30a   Cyclooctyl      H      single bond   5                                  31a   Cyclododecyl    H      single bond   5 --                               32a   4-tert.-Butylcyclohexyl                                                                       H      single bond   5 --                               33a   4-Isopropylcyclohexyl                                                                         H      single bond   5 --                               34a   3-Trifluoromethylcyclohexyl                                                                   H      single bond   5 --                               35a   3,3-Dimethylcyclohexyl                                                                        H      single bond   5 --                               36a   Cyclohexyl      Cyclohexyl                                                                           single bond   5 --                               37a   Cyclohexyl      H      CH.sub.2      5 --                               38a   Cyclopentyl     H      CH.sub.2      5 --                               39a   Cyclooctyl      H      CH.sub.2      5 --                               40a   Cyclododecyl    H      CH.sub.2      5 --                               41a   4-tert.-Butylcyclohexyl                                                                       H      CH.sub.2      5 --                               42a   4-Isopropylcyclohexyl                                                                         H      CH.sub.2      5 --                               43a   3-Trifluoromethylcyclohexyl                                                                   H      CH.sub.2      5 --                               44a   3,3-Dimethylcyclohexyl                                                                        H      CH.sub.2      5 --                               45a   Cyclohexyl      Cyclohexyl                                                                           CH.sub.2      5 --                               46a   Cyclohexyl      H      single bond   6 --                               47a   Cyclopentyl     H      single bond   6 --                               48a   Cyclooctyl      H      single bond   6 --                               49a   Cyclododecyl    H      single bond   6 --                               50a   4-tert.-Butylcyclohexyl                                                                       H      single bond   6 --                               51a   4-Isopropylcyclohexyl                                                                         H      single bond   6 --                               52a   3-Trifluoromethylcyclohexyl                                                                   H      single bond   6 --                               53a   3,3-Dimethylcyclohexyl                                                                        H      single bond   6 --                               54a   Cyclohexyl      Cyclohexyl                                                                           single bond   6 --                               55a   p-tert.-Butylbenzyl                                                                           H      NH            6 --                               56a   p-tert.-Butylbenzyl                                                                           Butyl  NH            6 --                               57a   p-tert.-Butylbenzyl                                                                           Cyclohexyl                                                                           NH            6 --                               58a   p-(1,1,2-Trimethylpropyl)benzyl                                                               H      NH            6 --                               59a   p-(1,1,2-Trimethylpropyl)-                                                                    Cyclooctyl                                                                           NH            6 --                                     benzyl                                                                  60a   p-tert.-Butoxybenzyl                                                                          H      NH            6 --                               61a   p-tert.-Butoxybenzyl                                                                          Cyclohexyl                                                                           NH            6 --                               62a   p-tert.-Butylbenzyl                                                                           H      NH            8 --                               63a   p-tert.-Butylbenzyl                                                                           Cyclohexyl                                                                           NH            8 --                               64a   p-tert.-Butylbenzyl                                                                           Cyclooctyl                                                                           NH            8 --                               65a   p-Isopropylbenzyl                                                                             H      NH            8 --                               66a   p-Isopropylbenzyl                                                                             1,3-Dimethyl-                                                                        NH            8 --                                                     butane                                                  67a   p-Methoxybenzyl H      NH            8 --                               68a   p-Methoxybenzyl Propyl NH            8 --                               69a   p-tert.-Butylbenzyl                                                                           H      single bond   5 --                               70a   p-tert.-Butylbenzyl                                                                           Cyclohexyl                                                                           single bond   5 --                               71a   p-Ethoxybenzyl  H      single bond   5 --                               72a   p-Ethoxybenzyl  Isopropyl                                                                            single bond   5 --                               73a   p-tert.-Butylbenzyl                                                                           H      CH.sub.2      5 --                               74a   p-tert.-Butylbenzyl                                                                           Cyclohexyl                                                                           CH.sub.2      5 --                               75a   p-tert.-Butylbenzyl                                                                           Cyclooctyl                                                                           CH.sub.2      5 --                               76a   p-(1,1,2-Trimethylpropyl)-                                                                    H      CH.sub.2      5 --                                     benzyl                                                                  77a   p-(1,1,2-Trimethylpropyl)-                                                                    Cyclooctyl                                                                           CH.sub.2      5 --                                     benzyl                                                                  78a   p-tert.-Butoxybenzyl                                                                          H      CH.sub.2      5 --                               79a   p-tert.-Butoxybenzyl                                                                          1,2-Dimethyl-                                                                        CH.sub.2      5 --                                                     propyl                                                  80a   p-tert.-Butylbenzyl                                                                           H      single bond   6 --                               81a   p-tert.-Butylbenzyl                                                                           Butyl  single bond   6 --                               82a   p-tert.-Butylbenzyl                                                                           Cyclohexyl                                                                           single bond   6 --                               83a   p-tert.-Butoxybenzyl                                                                          H      single bond   6 --                               84a   p-tert.-Butoxybenzyl                                                                          Cyclohexyl                                                                           single bond   6 --                               85a   Cyclohexyl      H      NMe           6 --                               86a   Cyclohexyl      H      NCH.sub.2 Ph  8 --                               87a   p-tert.-Butylbenzyl                                                                           H      NMe           6 --                               88a   p-tert.-Butylbenzyl                                                                           H                                                                                     ##STR22##    8 --                               __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________     ##STR23##                                                                     Comp. No.                                                                           ##STR24##                                                                               X             n                                                                               HY    m.p./IR (film) [cm.sup.-1 ]            __________________________________________________________________________     1b                                                                                  ##STR25##                                                                              NH            6 HCl   195° C.                           2b                                                                                  ##STR26##                                                                              NH            6 CH.sub.3 COOH                                                                       3165, 3051, 2933, 2858, 1679, 1560,                                           471, 1402, 1286                          3b                                                                                  ##STR27##                                                                              NH            6 C.sub.2 H.sub.2 O                                                                   100° C.                           4b                                                                                  ##STR28##                                                                              NH            6 --                                             5b                                                                                  ##STR29##                                                                              NH            6 HI    3225, 2930, 1643, 1316                   6b                                                                                  ##STR30##                                                                              NH            6 --                                             7b                                                                                  ##STR31##                                                                              NH            6 --                                             8b                                                                                  ##STR32##                                                                              NH            6 --                                             9b                                                                                  ##STR33##                                                                              NH            8 --                                            10b                                                                                  ##STR34##                                                                              NH            8 HI    3218, 2926, 2854, 1643, 1316            11b                                                                                  ##STR35##                                                                              NH            8 HCl   3308, 3236, 3160, 3057, 2929, 2853,                                           812, 1654, 1634, 1314                   12b                                                                                  ##STR36##                                                                              NH            8 CH.sub.3 COOH                                                                       3227, 3160, 2927, 2854, 1667, 1567,                                           441, 1398, 1318                         13b                                                                                  ##STR37##                                                                              NH            8 C.sub.2 H.sub.2 O.sub.4                                                             140° C.                          14b                                                                                  ##STR38##                                                                              NH            8 --                                            15b                                                                                  ##STR39##                                                                              NH            8 --                                            16b                                                                                  ##STR40##                                                                              NH            8 --                                            17b                                                                                  ##STR41##                                                                              NH            8 --                                            18b                                                                                  ##STR42##                                                                              single bond   5 --                                            19b                                                                                  ##STR43##                                                                              single bond   5 --                                            20b                                                                                  ##STR44##                                                                              single bond   5 --                                            21b                                                                                  ##STR45##                                                                              single bond   5 --                                            22b                                                                                  ##STR46##                                                                              single bond   5 --                                            23b                                                                                  ##STR47##                                                                              CH.sub.2      5 --                                            24b                                                                                  ##STR48##                                                                              CH.sub.2      5 --                                            25b                                                                                  ##STR49##                                                                              CH.sub.2      5 --                                            26b                                                                                  ##STR50##                                                                              CH.sub.2      5 --                                            27b                                                                                  ##STR51##                                                                              CH.sub.2      5 --                                            28b                                                                                  ##STR52##                                                                              single bond   6 --    3284, 2916, 2849, 1637, 1612, 1556,                                           470, 1262                               29b                                                                                  ##STR53##                                                                              single bond   6 HJ    197° C.                          30b                                                                                  ##STR54##                                                                              single bond   6 HCl   3290, 3142, 3063, 3001, 2984, 2926,                                           862, 2853, 1674, 1590                   31b                                                                                  ##STR55##                                                                              single bond   6 CH.sub.3 COOH                                                                       2926, 2854, 1677, 1560, 1396, 1285      32b                                                                                  ##STR56##                                                                              single bond   6 --    156-158° C.                      33b                                                                                  ##STR57##                                                                              single bond   6 HCl   3214, 3067, 2926, 2854, 1646, 1317      34b                                                                                  ##STR58##                                                                              single bond   6 HI    3217, 2925, 2853, 1642, 1315            35b                                                                                  ##STR59##                                                                              single bond   6 CH.sub.3 COOH                                                                       3231, 2928, 2855, 1660, 1558, 1275      36b                                                                                  ##STR60##                                                                              single bond   6 C.sub.2 H.sub.2 O.sub.4                                                             140-142° C.                      37b                                                                                  ##STR61##                                                                              single bond   6 --                                            38b                                                                                  ##STR62##                                                                              single bond   6 --                                            39b                                                                                  ##STR63##                                                                              single bond   6 --                                            40b                                                                                  ##STR64##                                                                              NMe           8 --                                            41b                                                                                  ##STR65##                                                                               ##STR66##    6 --                                            __________________________________________________________________________

The compounds are suitable as fungicides.

The fungicidal compounds and the agents containing them can be applied,for example, in the form of directly sprayable solutions, powders,suspensions, including concentrated aqueous, oily or other suspensionsor dispersions, emulsions, oily dispersions, pastes, dusts, broadcastingagents or granules by spraying, atomizing, dusting, broadcasting orwatering. The modes of application depend on the purposes for which theyare used; they should ensure in all cases the finest possible dispersionof the active ingredients according to the invention.

The plants are normally sprayed or dusted with the active ingredients orthe seeds of the plants are treated with the active ingredients.

The formulations are prepared in a conventional manner, for example bydiluting the active ingredient with solvents and/or carriers, if desiredusing emulsifiers and dispersants, it being possible when water is usedas diluent also to add organic solvents as cosolvents. Auxiliariessuitable for this purpose are essentially: solvents such as aromaticcompounds (e.g. xylene), chlorinated aromatic compounds (e.g.chlorobenzenes), paraffins (e.g. petroleum fractions), alcohols (e.g.methanol, butanol), ketones (e.g. cyclohexanone), amines (e.g.ethanolamine, dimethylformamide) and water; carriers such as naturalrock meals (e.g. kaolins, aluminas, talc, chalk) and synthetic rockmeals (e.g. highly disperse silica, silicates); emulsifiers such asnonionic and anionic emulsifiers (e.g. polyoxyethylene fatty alcoholethers, alkylsulfonates and arylsulfonates) and dispersants such aslignin sulfite waste liquors and methylcellulose.

Suitable surfactants are alkali metal, alkaline earth metal and ammoniumsalts of aromatic sulfonic acids, e.g. lignin-, phenol-, naphthalene-and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- andalkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, andsalts of sulfated hexa-, hepta- and octadecanols, and of fatty alcoholglycol ethers, products of the condensation of sulfonated naphthaleneand its derivatives with formaldehyde, of naphthalene or ofnaphthalenesulfonic acids with phenol and formaldehyde, polyoxyethyleneoctylphenol ethers, ethoxylated isooctyl-, octyl- or nonylphenol,alkylphenol and tributylphenyl polyglycol ethers, alkylaryl polyetheralcohols, isotridecyl alcohol, fatty alcohol/ethylene oxide condensates,ethoxylated castor oil, polyoxyethylene alkyl ethers orpolyoxypropylene, lauryl alcohol polyglycol ether acetate, sorbitolesters, lignin sulfite waste liquors or methylcellulose.

Powders, dusts and broadcasting agents can be prepared by mixing ormilling together the active substances with a solid carrier.

Granules, e.g. coated, impregnated or homogeneous granules, can beprepared by binding the active ingredients to solid carriers. Solidcarriers are mineral earths such as silica gel, silicic acids,silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay,dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesiumoxide, milled synthetic materials, fertilizers such as ammonium sulfate,ammonium phosphate, ammonium nitrate, urea and vegetable products suchas cereals meal, bark, wood and nutshell meals, cellulose powder orother solid carriers.

Examples of such formulations are:

I. a solution of 90 parts by weight of compound No. 12a and 10 parts byweight of N-methyl-α-pyrrolidone, which is suitable for use in the formof very small droplets;

II. a mixture of 20 parts by weight of compound No. 14a, 80 parts byweight of xylene, 10 parts by weight of the adduct of 8 to 10 moles ofethylene oxide and 1 mole of oleic acid N-monoethanolamide, amide, 5parts by weight of calcium dodecylbenzenesulfonate, 5 parts by weight ofthe adduct of 40 moles of ethylene oxide and 1 mole of castor oil; thesolution is finely dispersed in water;

III. an aqueous dispersion of 20 parts by weight of compound No. 30b, 40parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20parts by weight of the adduct of 40 moles of ethylene oxide and 1 moleof castor oil;

IV. an aqueous dispersion of 20 parts by weight of compound No. 31b, 25parts by weight of cyclohexanol, 65 parts by weight of a mineral oilfraction of boiling point 210 to 280° C. and 10 parts by weight of theadduct of 40 moles of ethylene oxide and 1 mole of castor oil;

V. a mixture, milled in a hammer mill, of 80 parts by weight of compoundNo. 35b, 3 parts by weight of sodium diisobutylnaphthalene-α-sulfonate,10 parts by weight of the sodium salt of a ligninsulfonic acid from asulfite waste liquor and 7 parts by weight of powdered silica gel; themixture is finely dispersed in water to give a sprayable composition;

VI. an intimate mixture of 3 parts by weight of compound No. 31b and 97parts by weight of finely divided kaolin; this dust contains 3% byweight of active ingredient;

VII. an intimate mixture of 30 parts by weight of compound No. 12a, 92parts by weight of powdered silica gel and 8 parts by weight of liquidparaffin which has been sprayed onto the surface of this silica gel;this preparation confers good adhesion on the active ingredient;

VIII. a stable aqueous dispersion of 40 parts by weight of compound No.14a, 10 parts by weight of the sodium salt of a phenolsulfonicacid/urea/formaldehyde condensate, 2 parts by weight of silica gel and48 parts by weight of water, which can be further diluted;

IX. a stable oily dispersion of 20 parts by weight of compound No. 14a,2 parts by weight of calcium dodecylbenzenesulfonate, 8 parts by weightof fatty alcohol polyglycol ether, 20 parts by weight of the sodium saltof a phenolsulfonic acid/urea/formaldehyde condensate and 68 parts byweight of a paraffin mineral oil.

The compounds have excellent activity against a wide spectrum ofphytopathogenic fungi, especially from the Ascomycetes andBasidiomycetes classes. Some of them have systemic activity and can beemployed as leaf and soil fungicides.

They have particular importance for controlling a large number of fungion various crop plants such as wheat, rye, barley, oats, rice, corn,grass, cotton, soybean, coffee, sugar cane, grapevines, fruit andornamental plants and vegetable crops such as cucumbers, beans andgourds, as well as the seeds of these plants.

The compounds are applied by treating the fungi or the seeds, plants,materials or soil to be protected from fungal attack with a fungicidallyeffective amount of the active ingredients. Application takes placebefore or after infection of the materials, plants or seeds by thefungi.

The compounds are suitable for controlling the following specific plantdiseases:

Erysiphe graminis (powdery mildew) on cereals,

Erysiphe cichoracearum and Sphaerotheca fuliginea on gourds,

Podosphaera leucotricha on apples,

Uncinula necator on grapevines,

Puccinia species on cereals,

Rhizoctonia species on cotton and lawns,

Ustilago species on cereals and sugar cane,

Venturia inaequalis (scab) on apples,

Helminthosporium species on cereals,

Septoria nodorum on wheat,

Botrytis cinerea (gray mold) on strawberries and grapevines,

Cercospora arachidicola on peanuts,

Pseudocercosporella herpotrichoides on wheat and barley,

Pyricularia oryzae on rice,

Phytophthora infestans on potatoes and tomatoes,

Fusarium and Verticillium species on various crops,

Plasmopara viticola on grapevines,

Alternaria species on vegetables and fruit.

The novel compounds can also be used to protect materials (wood), e.g.against Paecilomyces variotii.

The fungicidal agents generally contain from 0.1 to 95, preferably from0.5 to 90, % by weight of active ingredient.

The application rates depend on the nature of the desired effect and arefrom 0.02 to 3 kg of active ingredient per ha.

Generally required for treating seeds is from 0.001 to 50 g, preferably0.01 to 10 g, of active ingredient per kilogram of seeds.

The fungicidal agents according to the invention can contain otheractive ingredients, e.g. herbicides, insecticides, growth regulators,fungicides or fertilizers. Mixing with fungicides in many cases resultsin an extension of the range of fungicidal activity. Use Example

Used for comparison was the active ingredient guazatine triacetate (A)disclosed in GB 1 114 155.

Activity on downy mildew of grapevines

Leaves of pot grapevines of the Muller Thurgau variety were sprayed withan aqueous sprayable composition which contained 80% of activeingredient and 20% of emulsifier in dry matter. In order to be able toassess the duration of action of the active ingredients, the plants wereplaced in a greenhouse for 8 days after the spray deposit had dried.Only then were the leaves infected with a suspension of zoo spores ofPlasmopara viticola (downy mildew of grapevines). The grapevines werethen placed initially in a chamber saturated with water vapor at 24° C.for 48 hours and then in a greenhouse at from 20° to 30° C. for 5 days.After this time, the plants were placed in the humid chamber for afurther 16 hours to increase the rate of sporangiophore discharge. Theextent of fungal attack was then assessed on the undersides of theleaves.

The result shows that active ingredients 12a, 14a, 30b and 31b whenapplied as a 0.025% strength (by weight) sprayable composition have abetter fungicidal action (95%) than the known active ingredient A (65%).

We claim:
 1. A substituted bisguanidine of the formula I ##STR67## whereR² is C₅ -C₁₀ -alkyl, C₃ -C₁₀ -alkenyl, C₃ -C₁₀ -alkynyl, C₁ -C₈-alkoxy-C₂ -C₈ -alkyl, C₃ -C₁₀ -haloalkenyl; or cycloalkyl which has5-12 carbon atoms in the ring and can carry up to three of the followingsubstituents: hydroxyl, C₁ -C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀-haloalkyl and C₁ -C₈ -alkoxy-C₁ -C₈ -alkyl; or benzyl which can besubstituted up to three times by C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkoxy, itbeing possible for these benzyl substituents also to carry a hydroxyl orC₁ -C₆ -alkoxy group, or the benzyl is substituted by C₁ -C₁₀-haloalkyl,R¹ is benzyl which can be substituted up to three times by C₁-C₁₀ -alkyl or C₁ -C₁₀ -alkoxy, it being possible for these benzylsubstituents also to carry a hydroxyl or C₁ -C₆ -alkoxy group, or thebenzyl is substituted by C₁ -C₁₀ -haloalkyl, X is CH₂, O, a single bond,NH, N-(C₁ -C₁₀ -alkyl) or N-benzyl whose phenyl can be substituted onceto three times by C₁ -C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl orhalogen, and n is 5 to 8,and its plant-compatible acid addition saltsand its metal complexes.
 2. A substituted bisguanidine according toclaim 1 wherein X is O.
 3. A substituted bisguanidine according to claim1 wherein X is NH.
 4. A substituted bisguanidine according to claim 1wherein X is N-(C₁ -C₁₀ -alkyl).
 5. A bisguanidine as claimed in claim 1wherein X is N-benzyl whose phenyl can be substituted one to three timesby C₁ -C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl or halogen.
 6. Asubstituted bisguanidine as claimed in claim 1 wherein R² is C₃ -C₁₀-alkeynl, C₃ -C₁₀ -alkynyl, C₁ -C₈ -alkoxy-C₂ -C₈ -alkyl, C₃ -C₁₀-haloalkenyl or cycloalkyl which has 5-12 carbon atoms in the ring andwhich can carry up to three of the following substituents: hydroxyl, C₁-C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl and C₁ -C₈ -alkoxy-C₁-C₈ -alkyl.
 7. A fungicide containing an effective amount of abisguanidine of the formula I ##STR68## R² is C₅ -C₁₀ -alkyl, C₃ -C₁₀-alkenyl, C₃ -C₁₀ -alkynyl, C₁ -C₈ -alkoxy-C₂ -C₈ -alkyl, C₃ -C₁₀-haloalkenyl; or cycloalkyl which has 5-12 carbon atoms in the ring andcan carry up to three of the following substituents: hydroxyl, C₁ -C₁₀-alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl and C₁ -C₈ -alkoxy-C₁ -C₈-alkyl; or benzyl which can be substituted up to three times by C₁ -C₁₀-alkyl or C₁ -C₁₀ -alkoxy, it being possible for these benzylsubstituents also to carry a hydroxyl or C₁ -C₆ -alkoxy group, or thebenzyl is substituted by C₁ -C₁₀ -haloalkyl,R¹ is benzyl which can besubstituted up to three times by C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkoxy, itbeing possible for these benzyl substituents also to carry a hydroxyl orC₁ -C₆ -alkoxy group, or the benzyl is substituted by C₁ -C₁₀-haloalkyl, X is CH₂, O, a single bond, NH, N-(C₁ -C₁₀ -alkyl) orN-benzyl whose phenyl can be substituted once to three times by C₁ -C₁₀-alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl or halogen, and n is 5 to8,or salt or its metal complex and a liquid or solid carrier.
 8. Aprocess for controlling fungi, which comprises allowing an effectiveamount of a bisguanidine of the formula I ##STR69## R² is C₂ -C₁₀-alkyl, C₃ -C₁₀ -alkenyl, C₃ -C₁₀ -alkynyl, C₁ -C₈ -alkoxy-C₂ -C₈-alkyl, C₃ -C₁₀ -haloalkenyl; or cycloalkyl which has 5-12 carbon atomsin the ring and can carry up to three of the following substituents:hydroxyl, C₁ -C₁₀ -alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl and C₁ -C₈-alkoxy-C₁ -C₈ -alkyl; or benzyl which can be substituted up to threetimes by C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkoxy, it being possible for thesebenzyl substituents also to carry a hydroxyl or C₁ -C₆ -alkoxy group, orthe benzyl is substituted by C₁ -C₁₀ -haloalkyl,R¹ is benzyl which canbe substituted up to three times by C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkoxy,it being possible for these benzyl substituents also to carry a hydroxylor C₁ -C₆ -alkoxy group, or the benzyl is substituted by C₁ -C₁₀-haloalkyl, X is CH₂, O, a single bond, NH, N-(C₁ -C₁₀ -alkyl) orN-benzyl whose phenyl can be substituted once to three times by C₁ -C₁₀-alkyl, C₁ -C₁₀ -alkoxy, C₁ -C₁₀ -haloalkyl or halogen, and n is 5 to8,or its salt or metal complex to act on fungi, plants at risk or fungalattack, their habitat or their seed, or on materials.